An Efficient Construction of CF₃‐Substituted Spirooxindole‐Fused Benzo[a]quinolizidines by a Three‐Component Cyclization

Abstract

Benzo[a]quinolizidine is a key subunit in numerous natural products and pharmaceuticals, and therefore its synthesis has received much attention in resent years. Described herein is a convenient three‐component cyclization for the efficient construction of CF3‐substituted spirooxindole‐fused benzo[a]quinolizidines by using CF3‐propiolate as a building block. This attractive protocol may find great synthetic utility since CF3‐containing complex structures were installed by a one‐step cyclization under mild conditions.

Recent Strategies in the Nucleophilic Dearomatization of Pyridines, Quinolines, and Isoquinolines

“…In 2021, the same groups extended the three-component cyclization to isatin derivatives 75 as dipolarophiles, for the synthesis of fluorinated spirooxindole-fused benzo[a] quinolizidines 196 in very good yields, albeit as equimolecular mixtures of diastereoisomers (Scheme 98, eq 3). 146 Nenajdenko and Trofimov explored the use of trifluoroacetylacetylenes as precursors of 1,3-dipoles. In 2018, they reported a reaction between quinolines, aryltrifluoroacetylacetylenes 197, and water in acetonitrile as the solvent, which rendered trifluoromethylated oxazinoquinolines 198 as single diastereoisomers in very good yields (Scheme 99, eq 1).…”

“…In 2021, the same groups extended the three-component cyclization to isatin derivatives 75 as dipolarophiles, for the synthesis of fluorinated spirooxindole-fused benzo[a] quinolizidines 196 in very good yields, albeit as equimolecular mixtures of diastereoisomers ( Scheme 98 , eq 3). 146 …”